Decreased vesicular acetylcholine transporter and α4β2 nicotinic receptor density in the rat brain following 192 IgG-saporin immunolesioning

Degeneration of cholinergic neurons is a well known characteristic of Alzheimer's disease (AD). Two radioligands were studied in a rat model of cholinergic degeneration to evaluate their potential efficacy for molecular imaging of AD. Following specific cholinergic-cell immunolesioning with 192 IgG-saporin (SAP), ex vivo autoradiography was performed with 123IBVM, a radioligand which targets the vesicular acetylcholine transporter (VAChT). Following the decay of 123I, the same animals had in vitro autoradiography performed with 125I-A-85380, a marker for nicotinic acetylcholine receptors (nAChRs). As expected significant, widespread decreases in 123IBVM uptake were observed in SAP treated animals. Moderate but significant reductions in 125I-A-85380 binding in the hippocampus (Hip) and cerebellum (Cbm) were also observed following SAP immunolesioning. The results with 123IBVM confirm and extend previous work investigating the uptake of radioiodinated IBVM in this animal model. The results with 125I-A-85380 are unique and are in contrast with work performed in this animal model with other nAChR radioligands, indicating the favourable properties of this radioligand for molecular imaging.